Differences in the effect on neural stem cells of fetal bovine serum in substrate-coated and soluble form

The influence of fetal bovine serum (FBS) adsorbed to poly(ethylene-co-vinyl alcohol) (EVAL) and polyvinyl alcohol (PVA) substrates (coated FBS) and FBS present in the culture medium (soluble FBS) on the behavior of embryonic rat cerebral cortical neural stem cells was studied at neurosphere level. When both coated FBS and soluble FBS were not present in the culture system, the fate and behavior of neurospheres were mediated mainly by the substrates used. When neurospheres were cultured either on FBS-coated EVAL or FBS-coated PVA substrates in the serum-free medium, the most striking morphological characteristic of neurospheres was that these neurosphere-forming cells attached and were induced to differentiate into process-bearing cell phenotypes predominantly; however, the differentiated cell phenotypes were dissimilar on these two substrates. On the contrary, when neurospheres were cultured in the medium containing 10% FBS, the neurosphere-forming cells were induced into protoplasmic cells typically but no difference in differentiated cell phenotypes on EVAL and PVA substrates was observed. Interestingly, instead of promoting process outgrowth under serum-free medium condition, coated FBS enhanced migration of differentiated protoplasmic cells when soluble FBS were present. These results inform that the substrates, coated serum, and soluble serum within the culture environment together can significantly alter cell behavior and morphological differentiation and will therefore be an important clue for the development of biomaterials to regulate the potential of the CNS neural stem cells.